[Arsenic trioxide induces socs-1 gene demethylation in myeloma cell lines].
The aim of this study was to explore the effect of arsenic trioxide (As(2)O(3)) on the methylation status of socs-1 gene in multiple myeloma cell lines U266, RPMI8226. The cell viability was assayed by MTT method. The methylation status of socs-1 gene was detected by methylation specific PCR. The expression of socs-1 gene mRNA was determined with real-time PCR. The cell apoptosis was analyzed by flow cytometry. The results indicated that hypermethylation of CpG island of socs-1 gene was observed without expression of socs-1 in myeloma cell lines U266, RPMI8226. The expression of socs-1 gene mRNA in each myeloma cell line increased significantly after exposure to As(2)O(3) for 72 hours as compared with the cell lines of wild type (p < 0.05). And cell proliferation was significantly inhibited, both early apoptosis and later apoptosis ratios increased in dose-dependent manner. It is concluded that As(2)O(3) may induce socs-1 demethylation and up-regulate the expression of the gene. This study provides a new thought and direction for exploring possible mechanism of cell apoptosis induced by As(2)O(3) and multiple myeloma treatment by As(2)O(3).
Wang
Ming-Ming
MM
Department of Hematology, Shanghai Ninth People Hospital, Shanghai Institute of Hematology, Shanghai 200011, China.
Zhu
Qi
Q
Ren
Zhi-Hong
ZH
Zou
Li-Fang
LF
Dou
Hong-Ju
HJ
Hu
Jun-Pei
JP
D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics*; D010087:Oxides / Q000494:pharmacology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
D001152:Arsenicals; D010087:Oxides; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000077237:Arsenic Trioxide